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Administrative data

Description of key information

The oral and dermal LD50 for Stearic acid, esters with methyl α-D-glucoside and the structural analouge Isostearic acid, esters with methyl α-D-glucoside were determined to be > 2000 mg/kg body weight in guideline studies according to OECD guidelines 401 and 402. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990-10-01 to 1990-10-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: - Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
February 24, 1987
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: no data
- Weight at study initiation: m: 221 - 237 g, f: 180 - 204 g
- Fasting period before study: from 16 h before study until 3 - 4 h after administration of the test item
- Housing: collective housing up to a maximum of 5 animals per cage (Macrolon type III)
- Diet: ad libitum, Ssniff-R Alleindiäten (pellets 2.5 cm long, 1.0 vm diameter), Ssniff Spezialdiäten GmbH, Soest/Westfalen, Germany
- Water: ad libitum, drinking water as for human consumption
- Acclimation period: at least 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2 °C
- Humidity (%): 50 - 85 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): artificial lighting (120 lux), 12/12


Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The test item was administered as a 20 % dispersion in aqua deionisata.
pH value: 7.62
Doses:
Range finding test: 2000 mg/kg bw
Main study: 2000 mg/kg bw
No. of animals per sex per dose:
Range finding test: 2 female animals
Main study: 10 (5 males, 5 females)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: 10 min, 2, 6, 24 h, and thereafter daily up to day 14
- Frequency of weighing: before treatment (day 0), and surviving animals were reweighed on days 7 and 14 (termination)
- Necropsy of survivors performed: yes (gross pathological examination)
- Other examinations performed: clinical signs, body weight
Statistics:
LD50 values were calculated according to Finney D.Y., Probit Analysis, 3rd. edition, Cambridge, 1997
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: no mortality
Mortality:
Range finding test: no mortalities
Main study: no mortalities
Clinical signs:
- No clinical signs
Body weight:
- Normal body weight gains
Gross pathology:
Lung: lung of one male marbled
Kidney: kidneys of 2 males marbled, of one male deformed with red spot on the surface
Genital system: 2 females with hydrometra in the uterus
The macroscopic changes observed were attributable to the sacrificing procedure or to minor variations which often occur spontaneously in rats of this strain and age.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
On the basis of the results obtained after a single oral administration, the oral LD50 of the test substance Stearic acid, esters with methyl α-D-glucoside (100 a.i.) was determined to be > 2000 mg/kg bw. The test substance was administered as a 20 % dispersion in water. No animal died. No clinical signs, effects on body weight were observed. The gross pathological findings were not test item dependent.
Executive summary:

In an acute oral toxicity study (limit test, according to OECD 401,1987), 5 male and 5 female Wistar rats were given a single oral dose of Stearic acid, esters with methyl α-D-glucoside (according to producer infromation 100 % a.i.) at a concentration of 2000 mg/kg bw and observed for 14 days. The test substance was administered as a 20 % dispersion in water.

Oral LD50 Males and Females > 2000 mg/kg bw.

No animal died. No clinical signs or effects on body weight were observed. Gross pathological examinations at 14days p.a. (terminal necropsy) revealed a marbled lung of one male rat. The kidney of one male was deformed with a red spot on the surface, two males had a marbles kidney. A hydrometra was found in the uterus of two femals. The findings were considered to be spontaneous and not test item dependent.

Stearic acid, esters with methyl α-D-glucoside (100 % a.i.) is practically non toxic at an oral dose of 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Data from a GLP compliant guideline study with reliability 1.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2008-08-06 to 2008-08-20
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across from a guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
1992
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: mean males: 243 g, mean females: 164 g ; variation did not exceed +/- 20 % of the sex mean
- Housing: in a controlled environment, individually housed in Macrolon cages (Mill type, height 18 cm)
- Diet: free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest,Germany)
- Water: ad libitum, tap water
- Acclimation period: at least 5 days before start of treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 3
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
- Area of exposure: approx. 10 % of the total body surface, i.e, approx. 25 cm2 for males and 18 cm2 for females.
- % coverage: 10 % of body surface
- Type of wrap if used: dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic
bandage. A piece of Micropore taps was additionally used for fixation of the bandages in females only.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin cleaned of residual test substance using tap water
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (2.02 ml/kg) body weight. Dose volume calculated as dose level (g/kg) / density (g/ml)
- The test substance was dosed undiluted as delivered by the sponsor.

Duration of exposure:
24 h
Doses:
2000 mg/kg (2.02 ml/kg) body weight.
Dose volume calculated as dose level (g/kg) / density (g/ml)
No. of animals per sex per dose:
5 males, 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: mortality: twice daily; body weight: days 1 (pre-administration), 8 and 15 and at death; clinical signs: at periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight



Statistics:
No
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
- One male was found dead on day 2. The death of one male on day 2 after treatment was considered to be spontaneous and not treatment related, no macroscopic abnormalities were found at necropsy.
Clinical signs:
- Piloerection was noted in all males and two females on day 1.
- Scales were seen in the treated skin-area of two females during the observation period (one female at day 4 and 5, the other at day 15, respectively) .
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
In this study the test substance has a LD50 of > 2000 mg/kg bw.
Executive summary:

In an acute dermal toxicity study according OECD guideline 402, 5 male and 5 female young adult Wistar rats were dermally exposed to Isostearic acid, esters with methyl α-D-glucoside. The test substance was dosed undiluted for 24 hours to 10 % of body surface area at a dose of 2000 mg/kg bw. Animals then were observed for 15 days.

Dermal LD50 males/females > 2000 mg/kg bw (limit test)

There were no treatment related clinical signs, necropsy findings or changes in body weight.

The death of one male on day 2 after treatment was considered to be spontaneous and not treatment related, no macroscopic abnormalities were found at necropsy.

The test substance Isostearic acid, esters with methyl α-D-glucoside is practically non-toxic.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Data from a read-across study RL1 with GLP are available.

Additional information

Acute toxicity oral:

In an acute oral toxicity study (limit test, according to OECD 401, 1987), 5 male and 5 female Wistar rats were given a single oral dose of 2000 mg/kg bw Stearic acid, esters with methylα-D-glucoside (100 % a.i.) and observed for 14 days.

No animal died. No clinical signs or effects on body weight were observed. The observed findings at gross pathological examinations were considered to be spontaneous and not test item related (marbled lung of one male rat, kidney of one male was deformed with a red spot on the surface; two males had a marbled kidney).

The oral LD50 of Stearic acid, esters with methylα-D-glucoside (100 % a.i) was determined to be > 2000 mg/kg body weight in.

 

Similar results were obtained from an acute oral toxicity study according to OECD guideline 423 in female rats on the read-across substance Isostearic acid, esters with methylα-D-glucoside (100 % a.i). No mortality occurred in this study. There were no treatment related clinical signs, necropsy findings or changes in body weight.

The oral LD50 of the read-across substance Isostearic acid, esters with methylα-D-glucoside (100 % a.i.) was dertermined to be > 2000 mg/kg bw in female rats.

 

Acute toxicity dermal:

In an acute dermal toxicity study according OECD guideline 402, 5 male and 5 female young adult Wistar rats were dermally exposed to Isostearic acid, esters with methylα-D-glucoside. The study was performed as limit test at a dose of 2000 mg/kg bw.

There were no treatment related clinical signs, necropsy findings or changes in body weight.

The death of one male on day 2 after treatment was considered to be spontaneous and not treatment related, no macroscopic abnormalities were found at necropsy.

The dermal LD50 of the read-across substance Isostearic acid, esters with methylα-D-glucoside was determined to be > 2000 mg/kg bw in this limit test.

 

Justification for read-across:

Read-across is considered acceptable, based on the structural analogue approach from Isostearic acid, esters with methylα-D-glucoside to Stearic acid, esters with methylα-D-glucoside.

Stearic acid, esters with methylα-D-glucoside is a reaction product of Methyl glucoside with Stearic acid, a linear saturated mainly C18 fatty acid whereas for Isostearic acid, esters with methylα-D- the branched Isostearic acid is used. Composition of chain length is very similar; more than 90 % of the fatty acids have a carbon number of 18, with some chain length distribution between C16 and C20.

The main components of Isostearic acid are mono- and poly branched C18 fatty acids, in which the branching occurs mainly medium-chained, mostly methylenic, which accounts for its good biodegradability. However, a defined structure of isostearic acid does not exist.

The reaction leads to a fatty acid ester in which the four OH-groups of glucose are partially esterified.

Due to its esterification with the branched Isostearic acid, isostearate is more hydrophobic than the sesquistearate.

Stearic acid, esters with methylα-D-glucoside is composed of Methylglucoside (2.4 %), Methyl glucoside ester (approx. 78 % mono-, di-, tri-, and tetraester (mainly di, and triester)) and of approx. 19 % free fatty acids. Whereas Isostearic acid, esters with methylα-D-glucoside is composed of Methylglucoside (4 %), Methyl glucoside ester (approx. 83 % mono-, di-, and triester (mainly diester)) and of approx. 13 % free fatty acids.

Likewise intrinsic toxicological properties of Stearic acid, esters with methylα-D-glucoside and Isostearic acid, esters with methylα-D-glucoside are proven for acute oral toxicity, skin and eye irritation, skin sensitization and genmutation in bacteria. The read-across substance Isostearic acid, esters withα-methyl glucose, containing branched chains, is considered to be more critical in its toxicological impacts and can be understood as a worst case in this analogue approach. However, no intrinsic toxicological property leading to an intrinsic health hazard could be identified for the Isostearic acid, esters withα-methyl glucose.

In conclusion this structural analogue approach is scientifically justified by close similarities of structural aspects and physico-chemical properties and finally the comparable harmless toxicological profile of both substances.

 

Acute toxicity inhalation:

Exposure of humans via inhalation is unlikely taking into account the low vapour pressure of the substance and/or low likelihood of the generation of aerosols, particles or fine dusts of an inhalable size. Stearic acid, esters with methylα-D-glucoside is a solid, marketed and used in form of Pellets about 5 - 8 mm in the diameter. Taking this consistence into account the generation of inhalable particles such as fine dust or aerosols is unlikely. Vaporization is not considerable due to the very low vapour pressure. Therefore inhalation is not a relevant route of exposure and testing by inhalation is not appropriate according to REACH-VO Annex VIII 8.5.2, Column 2.

 

 


Justification for selection of acute toxicity – oral endpoint
Data from a GLP compliant guideline studies with reliability 1, one with the substance itself and one with the read-across substance Isostearic acid, esters with methyl α-D-glucoside. No adverse effects were observed in both studies.

Justification for selection of acute toxicity – dermal endpoint
Data from a read-across study RL1 with GLP are available.

Justification for classification or non-classification

Data from an acute oral toxicity study according to OECD guideline 401 are available for Stearic acid, esters with methyl α-D-glucoside. Additionally data from the chemically closely related read-across substance Isostearic acid, esters with methyl α-D-glucoside are available from an acute oral toxicity study ( OECD 423) and a dermal toxicity study (OECD 402).

Based on the oral LD50 of > 2000 mg/kg bw and the dermal LD50 of 2000 mg/kg bw a non-classification for acute oral and dermal toxicity is justified according to CLP (EU-GHS) Regulation (EC) No1272/2008 as well as Directive 67/548/EEC.